Active and machine learning-based approaches to rapidly enhance microbial chemical production.

Journal: Metabolic engineering
Published Date:

Abstract

In order to make renewable fuels and chemicals from microbes, new methods are required to engineer microbes more intelligently. Computational approaches, to engineer strains for enhanced chemical production typically rely on detailed mechanistic models (e.g., kinetic/stoichiometric models of metabolism)-requiring many experimental datasets for their parameterization-while experimental methods may require screening large mutant libraries to explore the design space for the few mutants with desired behaviors. To address these limitations, we developed an active and machine learning approach (ActiveOpt) to intelligently guide experiments to arrive at an optimal phenotype with minimal measured datasets. ActiveOpt was applied to two separate case studies to evaluate its potential to increase valine yields and neurosporene productivity in Escherichia coli. In both the cases, ActiveOpt identified the best performing strain in fewer experiments than the case studies used. This work demonstrates that machine and active learning approaches have the potential to greatly facilitate metabolic engineering efforts to rapidly achieve its objectives.

Authors

  • Prashant Kumar
    Global Centre for Clean Air Research (GCARE), School of Engineering, Civil and Environmental Engineering, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford GU2 7XH, Surrey, United Kingdom; Institute for Sustainability, University of Surrey, Guildford GU2 7XH, Surrey, United Kingdom.
  • Paul A Adamczyk
    From the Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706.
  • Xiaolin Zhang
    Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Dr., Madison, WI, 53706, USA.
  • Ramon Bonela Andrade
    Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Dr., Madison, WI, 53706, USA.
  • Philip A Romero
    Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: promero2@wisc.edu.
  • Parameswaran Ramanathan
    Department of Electrical and Computer Engineering, University of Wisconsin-Madison, 1415 Engineering Dr., Madison, WI, 53706, USA. Electronic address: parmesh.ramanathan@wisc.edu.
  • Jennifer L Reed
    From the Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, jennifer.reed@wisc.edu.